This Core is directed towards the discovery of new anticancer agents against colon, breast, lung, prostate and multidrug resistant solid tumors. These are tumors which, in humans, have minimal responsiveness to current chemotherapeutic agents and are rarely cured once metastases have spread beyond the regional lymph nodes. The goal of this Core is to discover more effective agents for solid tumors, with its focus being the disk-diffusion, soft-agar, colony-formation assay which defines the specificity of test extracts, fractions and compounds in terms of their cytotoxic activity in vitro against leukemia L1210, murine colon carcinoma #38, murine mammary adenocarcinoma 17/Adr (a p-glycoprotein expressing, MDR phenotype tumor), human lung cancer H-125, human mammary cancer MX-1, human colon cancer H-116, and normal intestinal cells 118. The murine tumors are obtained directly from the mouse for use in the assay, thus maintaining biologic and rug response characteristics. The test extract or compound is not added directly to the cells but rather placed on a filter disk, which is placed on top of the soft agar containing the tumor or normal cells. Depending upon the innate sensitivity of the cells to the sample (and its concentration), a zone of inhibition f colony formation is quantified. Extracts with preferential cellular selectivity for the solid tumors will be evaluated against the same tumor in mice. Extracts which are equally active in this primary in vitro assay, move into a secondary in vitro assay which determines whether the compound is tumor selective. Such compounds also proceed to in vivo testing against an appropriate tumor model. The assay is quite suited to assessing crude extracts of natural products and chromatographic fractions (to aid the isolation chemist in the identification of the active compound). We plan to evaluate about 5,000 extracts, fractions and characterized natural products (and their analogs) each year.